Genuine and counterfeit prescription pill surveillance in Washington, D.C.

For the first time in Washington, D.C., an in-depth analysis of counterfeit pills has been performed as part of a larger initiative to understand the city's illicit drug supply. Over a 56-month period, 567 pills that were physically identified as a pharmaceutical were analyzed using gas chromatography mass spectrometry (GC-MS) and gas chromatography flame ionization detection (GC-FID). Out of the 567 pills submitted to our laboratory, 119 were confirmed to be counterfeit. Beginning in 2018, an increase in counterfeit pills was observed in suspected pharmaceutical submissions. By 2021, 62.5% of all pill exhibits were determined to be counterfeit. Most of the counterfeit pills submitted during this time frame had a '30M' imprint with blue coloring, consistent with the physical identification of a 30 mg Oxycodone tablet. Fentanyl was the number one identified psychoactive substance detected in counterfeit pills (75.4%), however, other opioids, precursors, and a novel benzodiazepine were also identified. This preliminary research hopes to illustrate counterfeit pill trends in Washington, D.C. and highlight the importance of analyzing pharmaceuticals in addition to suspected illicit substances. This surveillance is ongoing and collaboration with neighboring jurisdictions is anticipated in the future.

Analysis of drug residue in needle-exchange syringes in Washington, D.C.

For the first time in Washington, D.C., an analysis of drug residue from used needle-exchange syringes has been performed. This analysis is part of a larger initiative to understand the District of Columbia's illicit drug supply and its intravenous (IV) user's consumption trends as our nation faces the opioid epidemic. The goal of this study is to develop a more comprehensive monitoring program that provides real-time analysis necessary for public health organizations, in addition to providing initial observations of drugs detected. A total of 1187 syringes were analyzed over a period of nine months. Of these, 732 syringes (61.7%) were confirmed to contain a controlled dangerous substance (CDS). Fentanyl was detected in 490 syringes, the most observed CDS in all syringes analyzed. Heroin was the second most detected CDS, observed in 192 syringes. The third most detected CDS was cocaine, which was observed in 132 syringes, followed by the fourth most detected CDS, methamphetamine, observed in 82 syringes. Novel findings of this study include the first reported detections of methamphetamine, synthetic cathinones, and synthetic cannabinoids in used syringes in D.C. Ninety-seven syringes that contained no CDS contained a non-controlled substance of interest, such as diphenhydramine, xylazine, and etizolam. One limitation of this study is that this method cannot determine whether mixtures present in syringes stem from mixtures present prior to injection, back-to-back usage, or sharing of needles. This preliminary study illustrates the strength of surveillance to monitor drug trends and can be used to detect emerging novel dangerous substances in the future.

Photoemission ambient pressure ionization (PAPI) with an ultraviolet light emitting diode and detection of organic compounds.

The development of compact, rugged and low-power ion sources is critical for the further advancement of handheld mass analyzers. Further, there is a need to replace the common (63)Ni source used at atmospheric pressure with a non-radioactive substitute. We present here a description of a light emitting diode (LED) photoemission ionization source for use in mass spectrometry for the detection of volatile organic compounds. This technique relies upon the generation of photoelectrons from a low-work function metal via low-energy ultraviolet (UV) light (280 or 240 nm) generated by a single LED in air at atmospheric pressure. These low-energy photoelectrons result in either direct electron capture by the analyte or chemical ionization. Currently, only negative ions are demonstrated due to operation at atmospheric pressure. Ion generation occurs without use of high electric fields such as those found in corona discharge or electrospray ionization. This source is effective for measuring organic vapors from gases, liquids and surface residues via atmospheric pressure chemical ionization, initiated by photoemission off a conductive surface. Several classes of organic vapors are analyzed and found to be effectively detected, including compounds that ionize via electron attachment, dissociative electron capture, proton abstraction, adduct formation and replacement ionization.

Electrospray photoionization (ESPI) liquid chromatography/mass spectrometry for the simultaneous analysis of cyclodextrin and pharmaceuticals and their binding interactions.

We report on the use of a multimode electrospray ionization/atmospheric pressure photoionization source (ESI/APPI or ESPI for short) with liquid chromatography/mass spectrometry (LC/MS) to measure all components of a mixed-polarity liquid sample containing: (1) low-polarity component (hormone, pharmaceutical or sterol), (2) polar component (cyclodextrin substrate), and (3) bound polar complex. The ESPI source has several advantages over both single ESI and multimode electrospray ionization/chemical ionization (ESCI) analysis, including an enhanced bound-complex detection and better performance at lower solvent flow rates. Relative binding constants are determined with (i) ESI mode, resulting in relative R(ESI-MS) values, and (ii) both ESI and APPI modes, providing relative K(D) values. We find that low molecular-substitution (Ms) values of cyclodextrin, i.e., Ms = 0.4, preferentially bind to the low-polarity compounds tested. This investigation is intended to demonstrate the feasibility of ESPI as an additional tool for investigating mixed-polarity binding systems, providing mass-specific data for all solution components, both polar and non-polar.

Electrospray ionization/atmospheric pressure photoionization multimode source for low-flow liquid chromatography/mass spectrometric analysis.

Analysis of several polar and non-polar compounds is performed with a newly developed dual electrospray ionization/atmospheric pressure photoionization (ESI/APPI) or ESPI source. Several variables are considered in the source, such as ESI probe heater temperature, solvent flow, dopant effects, repeller plate voltage, source geometry and photon energy (Kr vs. Ar lamp). Direct photoionization resulting in a molecular radical cation [M](*+) dominates at high temperatures (>400 degrees C) and low flow rates (<200 microL/min). Indirect photo-induced chemical ionization (PCI) involving solvent molecules becomes important at lower temperatures and higher solvent flow rates. Indirect PCI is enhanced using an Ar lamp, which yields comparable [M+H](+) signal but poorer [M](*+) signal than the Kr lamp at lower temperatures and higher flow rates. This is in support of our recent finding that the Ar lamp results in a solvent-dependent enhancement of analyte molecules via PCI. Analysis of 12 compounds in methanol under low-flow conditions (10 microL/min) demonstrates that the dual ESPI source performs favorably for most compounds versus the standard ESCI source, and significantly better than ESCI for the analysis of unstable drugs, like flurbiprofen. Several factors contributing to the benefits of the ESPI source are the shared optimal geometry for ESI and APPI sources and soft ionization of APPI versus APCI.

Development of medium pressure laser ionization, MPLI. Description of the MPLI ion source.

A novel pulsed valve/ion source combination capable of time-resolved sampling from atmospheric pressure has been developed for use with laser ionization time of flight mass spectrometry. The source allows ionization extremely close to the nozzle of the pulsed valve, enabling ultra-sensitive detection of a number of compounds, e.g., NO, at mixing ratios <1 pptV. Furthermore, at analyte mixing ratios in the ppbV range, the temporal resolution of the system is in the sub-second regime, allowing time-resolved monitoring of highly dynamic and complex mixtures, e.g., human breath or reacting chemical mixtures in atmospheric smog chamber experiments. Rotational temperatures of approximately 50 K have been observed for analytes seeded in the supersonic jet expansion at a distance of 1 mm downstream of the nozzle orifice. The refinement of the original ion source has drastically reduced the impact of reflected laser light and the resultant electron impact signals previously observed. The general applicability of this technique is demonstrated here by coupling the source to commercially available as well as home-built time-of-flight mass spectrometers. Finally, we discuss the MPLI technique in view of the very recently introduced atmospheric pressure laser ionization (APLI) as well as the traditional jet-REMPI approach.